Sarkar D K, Friedman S J, Yen S S, Frautschy S A
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Washington.
Neuroendocrinology. 1989 Aug;50(2):204-10. doi: 10.1159/000125223.
The effect of preferential delivery of estradiol (E2) into the brain on both the hypothalamic-pituitary-ovarian axis and weight gain was studied in female rats. When E2 was coupled to a lipoidal dihydropyridine-pyridinium carrier, the resulting carrier E2 complex (CE), upon a single intravenous administration to cycling female rats, caused a dose-dependent inhibition of ovulation which lasted 3 times longer than with uncoupled E2. The dose of CE that delayed ovulation for 4 days was one twentieth the amount of E2 needed to produce the same effect. Studies in ovariectomized (OVEX) rats indicated that the prolonged ovulation-blocking action of CE appeared to be related to a sustained storage and release of E2 in the brain, which in turn suppressed the release of hypothalamic luteinizing hormone-releasing hormone (LHRH) and pituitary luteinizing hormone (LH). Upon single intravenous administration in pubertal female rats, CE caused a dose-dependent reduction of body weight gain for a minimum period of 28 days. The inhibitory action of CE on body weight gain was more potent and longer lasting than that of E2 in pubertal rats. When administered in OVEX rats, CE produced a loss of body weight that lasted significantly longer than that produced by uncoupled E2 in these rats. These results suggest that the biological action of E2 can be potentiated by this novel chemical delivery system.
在雌性大鼠中研究了雌二醇（E2）向脑内的优先递送对下丘脑 - 垂体 - 卵巢轴和体重增加的影响。当E2与脂质二氢吡啶 - 吡啶鎓载体偶联时，所得的载体E2复合物（CE）在对处于发情周期的雌性大鼠单次静脉内给药后，引起排卵的剂量依赖性抑制，其持续时间比未偶联的E2长3倍。使排卵延迟4天的CE剂量是产生相同效果所需E2量的二十分之一。对去卵巢（OVEX）大鼠的研究表明，CE延长的排卵阻断作用似乎与E2在脑内的持续储存和释放有关，这反过来又抑制了下丘脑促黄体生成激素释放激素（LHRH）和垂体促黄体生成激素（LH）的释放。在青春期雌性大鼠单次静脉内给药后，CE在至少28天的时间内引起体重增加的剂量依赖性降低。在青春期大鼠中，CE对体重增加的抑制作用比E2更强且持续时间更长。当在OVEX大鼠中给药时，CE导致体重减轻，其持续时间比这些大鼠中未偶联的E2引起的体重减轻持续时间长得多。这些结果表明，这种新型化学递送系统可以增强E2的生物学作用。
